What is the recommended starting dose and titration schedule of buspirone (BuSpar) for an adult with generalized anxiety disorder, including adjustments for hepatic impairment and elderly patients, administration instructions, and alternatives if ineffective?

Buspirone (BuSpar) Dosing for Generalized Anxiety Disorder

Start buspirone at 5 mg orally twice daily (10 mg/day total) and increase by 5 mg/day every 2-3 days as tolerated, targeting 15-30 mg/day in divided doses, with a maximum of 60 mg/day. 1

Standard Dosing Algorithm

Initial Dosing

• Begin with 5 mg orally twice daily (total 10 mg/day) 1, 2
• Administer doses approximately 12 hours apart for BID regimen 3

Titration Schedule

• Increase by 5 mg/day every 2-3 days based on response and tolerability 1
• Example progression: 5 mg BID → 7.5 mg BID → 10 mg BID → 15 mg BID 1

Target Therapeutic Dose

• 15-30 mg/day in divided doses (typically 7.5-15 mg twice daily) 1
• Can be administered as either twice daily (BID) or three times daily (TID) regimens with similar safety profiles 3
• BID dosing (15 mg twice daily) may offer better compliance without compromising tolerability 3

Maximum Dose

• 60 mg/day (20 mg three times daily) 1, 2

Critical Timing Consideration

Counsel patients that buspirone requires 2-4 weeks to achieve full anxiolytic effect 1, 4, 5. This delayed onset is a common pitfall—patients expecting immediate benzodiazepine-like relief may discontinue prematurely. The "lagtime" of 1-2 weeks necessitates active patient motivation and compliance support 4, 5.

Special Population Adjustments

Elderly Patients

• Start at 5 mg twice daily with no age-based dose adjustment required 1, 2
• Safety and efficacy profiles in 605 elderly patients (mean age 70.8 years) were similar to younger populations 2
• Pharmacokinetics are not affected by age 6

Hepatic Impairment

• Buspirone administration cannot be recommended in severe hepatic impairment 2
• Plasma levels increase 15-fold and half-life doubles in hepatic impairment compared to healthy individuals 2, 6
• If mild-moderate impairment, start at lowest dose (5 mg BID) and titrate very cautiously with extended intervals 2

Renal Impairment

• Buspirone administration cannot be recommended in severe renal impairment 2
• Cmax and AUC increase 2-fold in renal impairment after a single 20 mg dose 6
• For mild-moderate impairment, use conservative dosing with careful monitoring 2

Administration Instructions

Food Effects

• Administration with food increases buspirone exposure 2-fold (both Cmax and AUC) 6
• Maintain consistent administration timing relative to meals—either always with food or always without food 6
• This consistency prevents fluctuating plasma levels that could affect efficacy and tolerability

Drug Interactions Requiring Dose Adjustment

• Avoid or substantially reduce buspirone dose when coadministered with:
  • Verapamil, diltiazem, erythromycin, or itraconazole (substantially increase buspirone levels) 6
  • Rifampin decreases buspirone levels nearly 10-fold; may require dose increase 6
• Monitor prothrombin time if combined with warfarin 2

Alternatives if Ineffective

After Adequate Trial (4-6 Weeks at Target Dose)

• Consider benzodiazepines (diazepam, alprazolam, lorazepam) if immediate symptom relief is required, though these carry sedation and dependence risks 4, 5
• Buspirone may be particularly inappropriate for panic disorder—studies have been inconclusive, and it is not recommended for routine panic disorder treatment 5
• Buspirone appears most effective in patients with generalized anxiety disorder, chronic anxiety, anxious elderly, and mixed anxiety/depression 5

Key Safety Advantages

• Minimal sedation compared to benzodiazepines 4, 7
• No psychomotor or cognitive impairment, even when combined with alcohol 4
• No abuse potential, dependence, or withdrawal symptoms reported 7
• Most common adverse effects: dizziness, headache, nausea, nervousness, lightheadedness 7, 3

Critical Pitfall to Avoid

Discontinue buspirone at least 48 hours before urine catecholamine testing for pheochromocytoma—it interferes with urinary metanephrine/catecholamine assays, causing false-positive results 2.